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H Kishikawa

Publications and source records attributed to H Kishikawa.

At least 19 recordsLinked to original sources
PubMed1998

Retrospective study on the impact of hepatitis C virus infection on kidney transplant patients over 20 years.

BACKGROUND: The majority of chronic hepatitis is ascribable to hepatitis C virus (HCV) infection, whereas the clinical impact has not been understood in kidney transplant recipients. Our current study was carried out to assess the impact of HCV infection on kidney recipients over the long-term, and to investigate the effect and risk of interferon-alpha (IFN-alpha) therapy for chronic active hepatitis C. METHODS: Hepatitis B surface antigen (HBsAg) and antibody to HCV (HCVAb) were examined prospectively and retrospectively in 280 patients, who underwent kidney transplants in the period from 1973 to 1996. The patient survival rate, the graft survival rate, the incidence of liver dysfunction and the cause of mortality among the HCV infected and noninfected groups were analyzed. IFN-alpha therapy was performed on 10 patients with chronic active hepatitis C. RESULTS: Prevalence of the hepatitis virus was quite high at 34.3% (96/280): the frequency of the HBsAg carrier was 3.2% (9/280), that of the HCVAb carrier was 28.6% (80/280) and that of the both carriers was 2.5% (7/280). The other 184 cases (65.7%) were negative for both HBsAg and HCVAb. Liver dysfunction developed at the significantly higher incidence of 55% in HCVAb carriers compared to the 9.2% of the noninfected group (P<0.01). HCVAb carriers had a poor survival rate in the second decade compared to the noninfected group: 83.7% vs. 88.91% for 10-year survival (P=0.44) and 63.9% vs. 87.9% for 20-year survival (P<0.05). The poor survival rate was a result of the mortality from liver disorder. Five patients died of such disease in the infected groups whereas no noninfected patient died in the same period (p<0.01). As the result of IFN-alpha therapy, biochemical activity normalized or improved in eight cases, whereas the HCV-RNA titer was reduced only in three patients. Only one patient maintained normal biochemical markers and undetectable levels of HCV-RNA for 2 years after treatment. The therapy was discontinued for five patients with the adverse effects of acute rejection, deterioration of diabetes, and depression. CONCLUSIONS: HCV infection has a significant impact on kidney transplant recipients over the long term and in particular affects them in the second decade. Our pilot study revealed only partial efficacy of IFN-alpha therapy for HCV-infected recipients, but with the high risk of acute rejection.

Adult↗
PubMed1998

Differential production of interleukin-6 in the brain and spleen of mice treated with lipopolysaccharide in the presence and absence of lead.

The heavy metal lead (Pb) markedly augments the lethality of endotoxin in laboratory animals. Much of the tissue injury produced by endotoxin is thought to be mediated by cytokines. Thus, the effects of Pb on the regulation of interleukin-6 (IL-6), a proinflammatory cytokine that shows high correlation with symptoms of endotoxic shock, and the levels of corticosterone, a hormone produced to prepare the body to cope with stress, upon lipopolysaccharide (LPS; endotoxin) administration were investigated. After intravenous administration of LPS, the kinetics of IL-6 gene expression by Northern blot analysis revealed a rapid increase of IL-6 mRNA, which peaked by 2 h in the spleens and 3 h in the brains of B6C3F1 female mice, with or without Pb exposure. Peak production of IL-6 protein after LPS challenge was observed at 2 h in the spleens and 3 h in the sera regardless of Pb-treatment. However, Pb-exposed mice showed an altered kinetic profile of IL-6 appearance in the brain, in that the levels of IL-6 in the brains peaked at 4 h rather than 3 h, the peak for the control mice. Moreover, at two time points, the amounts of IL-6 were found to be higher in the brains of Pb-treated mice. Increases in IL-6 were detected in multiple areas of the brain, but Pb did not significantly enhance this level in any area. The observation of both IL-6 transcripts and protein in the brains of mice upon peripheral LPS administration is indicative of local de novo synthesis of IL-6 in the brain. IL-6 production in the brain may contribute to the centrally mediated effects of IL-6, since IL-6 in the brain is known to activate the hypothalamus-pituitary-adrenal (HPA) axis. Upon LPS challenge, corticosterone levels peaked at the 2-h time point and stayed elevated for 6 h regardless of Pb exposure. The increases in brain IL-6 and its extended expression by Pb do not appear to have significantly altered the HPA axis on the basis of the corticosterone level, but brain IL-6 is known to affect multiple brain functions such as long-term potentiation.

Animals↗
PubMed1998

A 20-year case study of a kidney transplant recipient with chronic active hepatitis C: clinical course and successful treatment for late acute rejection induced by interferon therapy.

BACKGROUND: The influence of hepatitis C virus (HCV) infection has been discussed in kidney transplantation. Our case study focused on four points: the clinical course of an HCV-infected recipient; the pathogenesis of hepatic disorders in such a patient; interferon (IFN)-alpha therapy; and the risk of IFN-alpha therapy. METHOD: A patient was suspected of acquiring HCV via transfusion at kidney transplant. He was examined several times serologically, virologically, endoscopically, and pathologically during a 20-year follow-up. RESULTS: Abnormal biochemical markers were found within a month after transplantation but recovery occurred without any treatment. Within 3 years postoperatively, hepatic disorder developed including peliosis hepatis, nodular regenerative hyperplasia, and cholestasis. These pathological conditions were ascribed to immunosuppressants: cyclophosphamide and azathioprine. Abnormal chemical markers decreased to normal values for 4 consecutive years with the substitution of cyclophosphamide and azathioprine for mizoribine. During the subsequent 13 years, the patient developed chronic hepatitis with clinical and morphological features of hepatitis C infection. Anti-HCV antibody was positive from the second post-transplant year and HCV genome was detected in the 17th year. IFN-alpha therapy was initiated in the 17th year and resulted in normal transaminase activities with no effect on viremia. However, acute cellular rejection developed. The rejection was steroid resistant but responsive to OKT3. CONCLUSION: HCV might remain latent for approximately 7 years even in kidney recipients unless toxic hepatitis occurs. Hepatotoxic drugs may cause a wide spectrum of liver diseases in HCV carriers as a result of the overload of immunosuppressants on hepatocytes. IFN-alpha could induce acute cellular rejection even in the 17th year. Such acute rejection can be reversible with OKT3.

Adult↗
PubMed1998

Cellular characterization of pituitary adenoma cell line (AtT20 cell) transfected with insulin, glucose transporter type 2 (GLUT2) and glucokinase genes: insulin secretion in response to physiological concentrations of glucose.

We investigated the mechanisms of insulin secretion by transfecting into a pituitary adenoma cell line (AtT20) a combination of genes encoding human insulin (HI), glucose transporter type 2 (GLUT2) and glucokinase (GK), followed by studying the characteristics of these cells. In static incubation, a cell line transfected with insulin gene alone (AtT20HI) secreted mature human insulin but this was not in a glucose-dependent manner. Other cell lines transfected with insulin and GLUT2 genes (AtT20HI-GLUT2-3) or with insulin and GK genes (AtT20HI-GK-1) secreted insulin in response to glucose concentrations of only less than 1 mmol/l. In contrast, cell lines transfected with insulin, GLUT2 and GK genes (AtT20HI-GLUT2-GK-6, AtT20HI-GLUT2-GK-7 and AtT20HI-GLUT2-GK-10) showed a glucose-dependent insulin secretion up to 25 mmol/l glucose. Glucose utilization and oxidation were increased in AtT20HI-GLUT2-GK cell lines but not in AtT20HI, AtT20HI-GLUT2-3 and AtT20HI-GK-1 cells at physiological glucose concentrations, compared with AtT20 cells. Diazoxide, nifedipine and 2-deoxy glucose suppressed (p < 0.05) glucose stimulated insulin secretion in AtT20HI-GLUT2-GK-6 cells. Glibenclamide, KCl or corticotropin releasing factor (CRF) stimulated (p < 0.05) insulin secretion both in AtT20HI and AtT20HI-GLUT2-GK-6 cells. Insulin secretion stimulated by glibenclamide, KCl or CRF was further enhanced by the addition of 25 mmol/l glucose in AtT20HI-GLUT2-GK-6 cells but not in AtT20HI cells. In perifusion experiments, a stepwise increase in glucose concentration from 5 to 25 mmol/l stimulated insulin secretion in AtT20HI-GLUT2-GK cell lines but the response lacked a clear first phase of insulin secretion. Our results suggest that both GLUT2 and glucokinase are necessary for the glucose stimulated insulin secretion in at least rodent cell lines, and that other element(s) are necessary for a biphasic insulin secretion typically observed in beta cells.

Adenoma↗
PubMed1998

Secretory carcinoma of the breast in an elderly woman: report of a case.

We herein report a case of secretory carcinoma of the breast in a 73-year-old woman. Secretory carcinoma is an extremely rare tumor and demonstrates distinctive pathologic characteristics. This tumor frequently occurs in either children or adolescents, and thus has been called juvenile carcinoma. We encountered this rare tumor in an elderly woman. Aspiration biopsy cytology was performed twice, but the cytological diagnosis was not carcinoma. Such pathologic characteristics as mild atypia, the absence of hyperchromasia, and a minimal degree of pleomorphism in the tumor cells can thus lead to a cytological misdiagnosis. An excisional biopsy was performed and secretory carcinoma was finally diagnosed. Consequently, a modified radical mastectomy (Kodama's method) was performed 7 days later. We describe this very rare tumor's clinicopathologic characteristics.

Age Factors↗
PubMed1998

Effect of combined administration of lansoprazole and sofalcone on microvascular and connective tissue regeneration after ethanol-induced gastric mucosal damage.

We undertook the present study to clarify the alteration of localization of basic fibroblast growth factor (bFGF), endothelial cells, and myofibroblasts in the healing of ethanol-induced gastric mucosal damage by the combined administration of lansoprazole and sofalcone. Wistar strain male rats were used. Ethanol 50% was given through orogastric intubation. Thirty minutes later, an aqueous solution of lansoprazole, sofalcone, a combination of lansoprazole and sofalcone, or physiologic saline was given orally. The stomach was removed and the localization of bFGF, myofibroblast, and endothelial cells was examined using monoclonal antibodies. Some rats were pretreated with indomethacin to rule out the effect of endogenous prostaglandin. The combined administration of lansoprazole and sofalcone brought about increased concentrations and immunoreactive areas of bFGF and a greater number of endothelial cells, compared with the ethanol-alone treatment. The number of myofibroblasts increased more significantly in the group treated with a combination of agents than in that treated with ethanol alone, ethanol plus sofalcone, or ethanol plus lansoprazole. Indomethacin pretreatment partly abolished the effects of single and combined administration of these agents. In conclusion, the mixed administration of lansoprazole and sofalcone accelerated the microvascular and connective tissue regeneration during the healing of ethanol-induced gastric mucosal damage.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

A prospective comparative trial of a gonadotropin-releasing hormone analogue with clomiphene citrate for the treatment of oligoasthenozoospermia.

BACKGROUND: We undertook a prospective trial to compare the efficacy and adverse effects of a gonadotropin releasing-hormone analogue (GnRHa) and clomiphene therapy for idiopathic normogonadotropic oligoasthenozoospermia (INOA). METHODS: Between January and December 1995, 44 newly-diagnosed INOA patients were randomly allocated to treatment with GnRHa or clomiphene citrate. Efficacy was assessed by measuring changes in semen parameters prior to and after 3 months of treatment. Twenty-three INOA patients underwent GnRHa therapy with 15 microg of diluted buserelin acetate given once a day intranasally, and 21 INOA patients were treated with 50 mg of clomiphene citrate daily by oral administration. RESULTS: The mean sperm density in the GnRHa group increased from 16.1 x 10(6)/mL to 26.9 x 10(6)/mL (P < 0.05), while the mean sperm density did not change significantly in the group treated with clomiphene. Similarly, the mean sperm motility increased from 35.9% to 43.9% in the GnRHa group (P < 0.05), but did not significantly change in the clomiphene group. No adverse effects were observed in either group. CONCLUSION: This GnRHa treatment protocol can be administered as an outpatient and is hoped to benefit INOA patients.

Administration, Intranasal↗
PubMed1998

Malignant neoplasm in kidney transplantation.

BACKGROUND: The kidney recipient is at a higher risk for cancer than is the general population, although the incidence of neoplasms in general is considered lower in Japan than in Western countries. The cause of this increased risk associated with either transplantation or geography has not yet been established. METHOD: The incidences and sites of malignant neoplasms were analyzed in 285 kidney recipients, who had been followed up for 3007 patient-years. The relationship between immunosuppressive states, the numbers of CD4-positive T lymphocytes, and the presence of malignant neoplasms was studied retrospectively. RESULTS: Eighteen malignant neoplasms were found in 17 of the 285 patients (6%). The malignancies developed in these patients an average of++ 1 26.5 months after transplantation. The incidence was only 3.9% at 10 years, increasing to 13.9% at 20 years. No difference in the time-course incidence was found between azathioprine-based and cyclosporin-based immunosuppressive regimens. The malignancies developed in the digestive organs in more than half of the patients, and were mainly in the liver, colon and rectum, and stomach, with a relatively low incidence of skin cancer and lymphoma. There was only one case of Epstein-Barr virus genome found in 5 specimens that were tested. Concerning the immunosuppressive state, CD4-positive T lymphocyte counts were not related directly with malignancies in our series. CONCLUSION: The cumulative incidence of malignancy increased markedly in the second posttransplant decade. The site of cancers in kidney recipients mirrors that of general Japanese malignancies. Our results revealed neither the cause nor predictor for malignancies in kidney transplant patients.

Adolescent↗
PubMed1998

Suppressive effect of simvastatin on intramural small coronary arterial lesions in cholesterol-fed rabbits.

The aim of this study was to examine the suppressive effect of simvastatin on intramural coronary arterial lesions in cholesterol-fed rabbits. In one experiment, six groups of rabbits were fed laboratory chow alone or with added 0.1%, 0.2%, 0.3%, 0.5% or 1.0% cholesterol for 16 weeks. In another experiment, four groups of rabbits were fed a 0.5% cholesterol diet and treated with simvastatin at 1, 3, or 5 mg/kg/day or placebo. In each rabbit, the levels of serum total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. In the two experiments, there were positive correlations between the lesion induction ratio and integrated TC (r=0.785, P<0.0001 and r=0.763, P<0.0001, respectively). The slopes of the regression lines for integrated TC obtained in the two experiments were similar, but the lesion induction ratio in the simvastatin-treated group was always lower, by about 14%, in comparison with that in the non-simvastatin-treated group. These findings suggest that simvastatin induces lesion reduction not only by reducing the levels of circulating cholesterol but also by directly suppressing the development of lipoidosis.

Animals↗
PubMed1998

Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6 myoblasts.

Previously we demonstrated that bradykinin infusion could increase glucose uptake into dog peripheral tissues, and that bradykinin could potentiate insulin-induced glucose uptake through glucose transporter 4 (GLUT4) translocation in dog adipocytes. However, skeletal muscle is the predominant tissue for insulin-mediated glucose disposal. The aim of this study was to determine how bradykinin affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes transformed from rat L6 myoblasts. The bradykinin receptor binding studies revealed that dog skeletal muscle and rat L6 myoblasts possessed significant numbers of bradykinin receptors (Kd = 88 and 76 pmol/l, Bmax = 82.5 and 20 fmol/mg protein respectively). An RT-PCR (reverse transcriptase-polymerase chain reaction) amplification showed mRNA specific for bradykinin B2 receptor in both cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated muscle and L6 myoblasts in the presence of insulin (10(-7) mol/l) in a dose-dependent manner, but not in the absence of insulin. Bradykinin also enhanced insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells. It is concluded that bradykinin could potentiate the insulin-induced glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6 myoblasts. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.

Animals↗
PubMed1998

Creation and characterization of a mitochondrial DNA-depleted pancreatic beta-cell line: impaired insulin secretion induced by glucose, leucine, and sulfonylureas.

It has been proposed that mitochondrial oxidative phosphorylation in pancreatic beta-cells plays an important role in insulin secretion. To examine the impact of mitochondrial dysfunction on insulin secretion, we created a MIN6 cell line that depleted mitochondrial DNA (mtDNA) by treatment with ethidium bromide (EtBr), and studied the response of the cell line to various secretagogues. MIN6 cells cultured with 0.5 microg/ml EtBr for over 2 months (termed MIN6 deltamt cells) revealed a marked (>90%) decrease in mtDNA content and a lack of mRNAs encoded by mtDNA. MIN6 deltamt cells showed the defects of cytochrome c oxidase activity, glucose- and leucine-induced increase in cellular ATP content, and respiratory chain-driven ATP synthesis, suggesting that MIN6 deltamt cells lost oxidative phosphorylation activity due to the selective disruption of the subunits of respiratory chain enzymes encoded by mtDNA. MIN6 deltamt cells also showed a decrease in glucose utilization, suggesting the impairment of the glycolytic pathway as well. After stimulation with glucose and leucine, MIN6 deltamt cells showed no response in insulin secretion or intracellular free Ca2+ concentration ([Ca2+]i). On the other hand, arginine stimulated insulin secretion and an increase in [Ca2+]i in MIN6 deltamt cells as in MIN6 cells. Glibenclamide also stimulated insulin secretion and an increase in [Ca2+]i in both types of cells, but the responses of MIN6 deltamt cells were significantly lower than those of MIN6 cells. These results suggest the importance of ATP production in insulin secretion and an increase in [Ca2+]i, both induced by glucose and leucine. Moreover, mitochondrial function turns out to be not essential but important for the activation of sulfonylurea-induced insulin secretion.

Adenosine Triphosphate↗
PubMed1998

[Direct effects of Chinese herbal medicine "hochuekkito" on sperm movement].

BACKGROUND AND PURPOSE: Chinese herbal medicine, "Hochuekkito" is widely used for male infertility in Japan. There have been many reports concerning its clinical usefulness but very few reports of in vitro experiments studying the mechanism of its effects. In addition to stimulating germ cells, we analyzed its direct effects on sperm using computer assisted semen analyzer (CASA). MATERIALS AND METHODS: Motile sperm were prepared using swim up technique from semen collected from ten healthy volunteers. Sperm movements (motility, velocity, linearity) were analyzed by CASA after adding either serum containing anti-sperm antibody (ASA) or normal serum with or without Hochuekkito. RESULTS: Two hours after adding serum with ASA, the decrease of sperm motility was significantly reduced from 25.1% (92.8%-->67.7%) to 12.5% (92.9%-->80.6%) by adding Hochuekkito. No significant difference in velocity and linearity was observed between two groups. By adding normal serum, any of three parameters differed significantly with or without Hochuekkito. CONCLUSION: Protective effects of Hochuekkito on sperm was suggested. Although normal sperm with ASA was used in this report, since the sperm of infertile patients are said to be more fragile, this results imply that direct protective effect is one of the mechanism of Hochuekkito for male infertility.

Adult↗
PubMed1998

[A welder with chemical pneumonitis caused by inhalation of zinc fume].

A 61-year-old man with a 32-year occupational history of welding developed malaise, cough, and dyspnea after inhalation of smoke while welding galvanized steel. On admission, peripheral leukocytosis, hypoxemia, and diffuse granular and linear opacities on a chest X-ray were present. The bronchioli were exaggerated in a chest high-resolution CT. Bronchoalveolar lavage revealed mild lymphocytosis and transbronchial lung biopsy showed siderosis and exudation of fibrin and neutrophils into alveolar spaces. The clinical and radiographic findings later improved except for an obstructive disorder on pulmonary function test. The respiratory health hazards associated with welding vary according to the materials and the concentration of inhaled substances. Acute chemical pneumonitis caused by inhalation of zinc fumes (zinc oxide) was accompanied by chronic siderosis in this case. It is well known that metal fume fever commonly occurs when inhaling zinc oxide fumes. However acute chemical pneumonitis after exposure to zinc oxide during welding has been only rarely reported.

Aerosols↗
PubMed1998

[A case of familial myoclonus showing extremely benign clinical course].

We report a patient with familial myoclonus showing an extremely benign clinical course. The patient was a 70-year-old woman, who first noticed shaking of hands at age of 25. The symptom did not worsen for more than 40 years. She visited our hospital at the age of 70 because of disturbance in chores because of worsening of her hand shaking in the past one year. A family history showed that 4 members had similar symptoms and that the two were afflicted with fits of loss of consciousness. On neurologic examination, rhythmic myoclonic jerks were noted in all the extremities, more in the upper limbs, both at rest and during action. Tandem gait was mildly disturbed. The remainings of neurologic examination were normal. SEP and jerk-locked back averaging provided evidence of cortical myoclonus. EEG showed multifocal polyspike discharges. Gene analysis for DRPLA, pyruvate and lactate levels in serum and the cerebrospinal fluid, serum amino acid levels, and CSF HVA and 5-HIAA levels were all normal. No brain atrophy was noted in cranial MRI. Myoclonus was markedly reduced after administration of clonazepam. The clinical features and electrophysiological data of our patient are consistent with the clinical diagnosis of familial essential myoclonus and epilepsy/benign adult familial myoclonic epilepsy.

Aged↗
PubMed1997

Interleukin-12 promotes enhanced resistance to Listeria monocytogenes infection of lead-exposed mice.

The heavy metal lead (Pb) has been shown to downregulate various parameters of cell-mediated immune (CMI) responses. This inhibition of CMI responses by Pb is exemplified by a higher mortality rate upon infections with sublethal doses of a variety of pathogens. Unlike Pb, which lowers host resistance, interleukin-12 (IL-12) exerts a substantial stimulatory influence on the host response to intracellular bacteria such as Listeria monocytogenes. To explore the influence of IL-12 in mice rendered susceptible to Listerial infection by oral exposure to Pb, we determined bacterial burdens and production of interferon gamma (IFN-gamma). As expected, Pb-exposed mice had increased morbidity due to higher Listerial titers as compared to control mice. However, administration of exogenous IL-12 reversed the Pb-induced inhibition of host defense and boosted the resistance of the non-Pb-treated mice. The enhanced CMI responses observed in both IL-12-treated groups were accompanied with elevations of IFN-gamma in the sera and spleens. Significant reduction in the number of viable Listeria in Pb-exposed mice upon IL-12 administration suggests that the processes downstream of IL-12 production were intact in the Pb-exposed mice and that the inhibition by Pb was due to the lack of functional IL-12. Alternatively, the exogenous IL-12 may have overcome a downstream effect by enhancing an secondary pathway. Support for the former hypothesis is based on the observation that Pb induced elevated levels of p40 splenic messenger RNA since increased p40 expression would result from lack of IL-12 formation. Contrary to the IFN-gamma levels, significantly higher levels of IL-6 and corticosterone were observed in the sera and spleens of Pb-exposed mice upon infection, suggesting heightened stress in the absence of IL-12. Overall, the results suggest that an environmental pollutant such as Pb can enhance the stress response, which naturally occurs during an infection, and can further compromise health by lowering host resistance by altering cytokine levels.

Animals↗